Laboratory Studies
Blood study results in patients with retroperitoneal fibrosis may include the following:
-
Elevated erythrocyte sedimentation rate (ESR)
-
Raised C-reactive protein (CRP) level
-
Raised urea and creatinine levels (50%-75%)
-
Normocytic normochromic anemia
-
Polyclonal hypergammaglobulinemia
-
Raised alkaline phosphatase level (has also been reported as a marker [5] )
-
Antinuclear antibodies (ANA; present in 60% of cases) [6]
Urinalysis results are usually normal. Rarely, microscopic hematuria or pyuria is observed.
Imaging Studies
Computed tomography (CT) scanning is the most frequently used imaging method for diagnosis and follow-up of retroperitoneal fibrosis. However, a number of other imaging methods can provide useful information. For example, positron emission tomography/magnetic resonance imaging (PET/MRI) has potential advantage for imaging small lesions, while offering reduced radiation exposure. [38] For complete discussion, see Retroperitoneal Fibrosis Imaging.
Plain radiography
Findings are nonspecific and usually due to the late complications. Abdominal films may show obliteration of the psoas shadow and an enlarged kidney outline due to hydronephrosis. Features of ankylosing spondylitis or metastasis may also be visible.
Chest radiography may demonstrate pulmonary edema or fibrosis. Mediastinal widening may result from a soft-tissue mass associated with mediastinal fibrosis.
Intravenous urography
The classic triad consists of the following [3, 39] :
-
Delay of contrast material with unilateral (20%) or bilateral (68%) hydronephrosis
-
Medial deviation of the middle third of the ureters (see the image below)
-
Tapering of the ureter at the level of L4/L5 vertebrae
Up to 18%-20% of control subjects may show this triad. [40]
Intravenous urogram in a patient with retroperitoneal fibrosis shows medial deviation of the middle part of both ureters.
Medial deviation of the ureter may result from retroperitoneal neoplasm, aneurysm, and bladder diverticulum.
Retrograde pyelography
Retrograde pyelography may show features similar to those described above. In addition, it may demonstrate poor distensibility of the ureters, as depicted in the images below.
Retrograde ureterogram in a patient with retroperitoneal fibrosis reveals smooth narrowing and medial shift of the ureter.
Retrograde pyelography delineates the pelvic calyceal anatomy and is usually performed prior to insertion of the stent to decompress the kidneys.
Interestingly, very little resistance is encountered during ureteric catheterization despite the extensive extrinsic fibrosis.
Lymphangiography
The retroperitoneal lymphatics are delicate and fine structures; therefore, they are more easily compressed by retroperitoneal fibrosis than by the adjacent blood vessels and ureters. Thus, lymphatic obstruction should precede ureteric compression.
Lymphangiography may show obstruction of lymphatic flow at L3/L4 level, opacification of collateral channels, nonvisualization of lymphatics above the L4 vertebra, and delay in passage of contrast through the iliac and para-aortic lymphatics. [41]
Ultrasonography
Ultrasonography is a simple noninvasive modality used to assess response to therapy. On a sonogram, retroperitoneal fibrosis appears as a retroperitoneal, extensive, well-defined, hypoechoic mass centered over the sacral promontory. The degree of hydronephrosis and hydroureter may vary.
Doppler ultrasonography has no role in differentiating benign from malignant retroperitoneal fibrosis. [42]
CT scanning
On unenhanced CT scans, retroperitoneal fibrosis appears as a plaque that is isodense with muscle and that envelops the aorta and inferior vena cava between the renal hila and sacral promontory and usually extends laterally to incorporate the ureters. Obliteration of the fat plane between the mass and the psoas muscle may be observed, as depicted in the images below.
Retroperitoneal fibrosis. Contrast-enhanced CT scan demonstrates a periaortic soft tissue attenuating mass.
Retroperitoneal fibrosis. Noncontrast CT scan shows periaortic fibrotic reaction associated with an inflammatory aortic aneurysm. Note bilateral ureteric stents.
Retroperitoneal hemorrhage, primary retroperitoneal sarcoma, metastatic deposits to the retroperitoneum, and retroperitoneal amyloidosis may show similar findings on CT scans. CT scan features that suggest malignant pathology include lateral displacement of the ureter, anterior displacement of the aorta, local bone destruction, and a large bulky lesion.
Elevation of the aorta from the spine is uncommon in benign retroperitoneal fibrosis. If present, it may be a sign of malignancy. [43]
After contrast injection, the plaque may show a variable degree of enhancement, depending on the stage of the disease. Enhancement is usually significant in the early active vascular stage. On the other hand, enhancement is poor in the late vascular stage.
Magnetic resonance imaging
Both benign and malignant retroperitoneal fibrosis have low-to-intermediate signal density on T1-weighted images and density on T2-weighted images that varies based on the disease stage. During the early stage, signal density is high because of high fluid content and hypercellularity. In contrast, late-stage disease has low T2 signal intensity as a result of avascular acellular fibrosis and decreased fluid content. [44] Steroid therapy may lead to similar changes because of decreased tissue edema.
Inhomogeneity of signal intensity on T2-weighted images may suggest malignancy; however, differentiation between benign and malignant retroperitoneal fibrosis on MRI is difficult, and biopsy is usually required to confirm the diagnosis. [33]
One study assessed delayed gadolinium enhancement ratios by comparing retroperitoneal fibrosis enhancement with that of psoas muscle. The dynamic enhancement ratio in acute retroperitoneal fibrosis significantly differed from the ratio in chronic retroperitoneal fibrosis. Dynamic gadolinium enhancement may be useful in differentiating newly diagnosed retroperitoneal fibrosis from treated chronic disease and may have a role in assessing disease activity, monitoring response to treatment, and detecting relapse. [45]
MRI has some advantages over CT scanning, including multiplanar capability, independence of renal function, and absence of radiation.
Positron emission tomography
Positron emission tomography (PET) scanning with 18F-fluorodeoxyglucose (18F-FDG) is a functional imaging modality that has proved useful in the evaluation of retroperitoneal fibrosis. 18F-FDG identifies areas of high glucose metabolic activity. Because inflammatory cells have an increased glucose uptake, high levels of glucose metabolism are seen in a retroperitoneal mass associated with retroperitoneal fibrosis if inflammation is present.
However, uptake of 18F-FDG by retroperitoneal fibrosis tends be lower than that by malignancy. A study of 18F-FDG PET/CT by Wang et al found that lesions of idiopathic retroperitoneal fibrosis displayed a lower frequency of high 18F-FDG uptake than retroperitoneal malignancies (P = 0.017) and a lower mean maximum standardized uptake value (SUVmax). [46]
No noninvasive method can reliably assess disease activity. However, 18F-FDG may be more reliable than acute phase reactants (ie, ESR, CRP) for monitoring the course of retroperitoneal fibrosis and response to therapy. [47, 48] In addition, it can reveal other sites of disease (eg, thyroid, thorax) and may help to identify the most appropriate sites for retroperitoneal biopsy.
Histologic Findings
In 1948, Ormond described two histologic features in retroperitoneal fibrosis: an inflammatory early stage and a chronic stage. [49] In the early stage, an inflammatory infiltrate contains macrophages, lymphocytes, plasma cells, and occasional eosinophils; neutrophils are generally absent. The macrophages are often lipid-laden and contain areas of perivascular lymphocytic infiltrate composed of T cells and B cells. Generally, tissue is highly vascular with numerous small blood vessels throughout.
In the chronic stage, the tissue becomes avascular and acellular with scattered calcification and progresses to fibrous scarring. [50] Occasionally, surrounding structures are invaded by retroperitoneal fibrosis. Invasion of the large veins may cause fibrous thickening of the intima, resulting in complete occlusion. Periaortic lymphatics may be blocked within the mass. Submucosal edema and lymphocytic infiltration may be observed in the ureter.
Corradi et al (2007) reported the presence of CD20 and CD3 cells, IgG4 plasma cells, and subtle vasculitic activity in idiopathic retroperitoneal fibrosis. [51]
In malignant retroperitoneal fibrosis, scattered nests of malignant cells are present within the inflammatory infiltrate. Hodgkin lymphoma and sclerosing retroperitoneal lymphomas are the most challenging differential diagnoses for the pathologist to exclude; Wu et al recommended the use of immunostains such as c-Kit, Leu-M1, Ki-1, LCA, and kappa and lambda light chain for that purpose. [52] See the table below.
Table. Differential Diagnoses of Retroperitoneal Fibrosis [51] (Open Table in a new window)
|
Retroperitoneal Fibrosis |
Retroperitoneal Lymphoma |
Sclerosing Mesenteritis |
Desmoid-Type Fibromatosis |
Inflammatory Myofibroblastic Tumor |
Well-Differentiated Liposarcoma Sclerosing Variant |
Ureteral displacement |
Medial |
Lateral |
|
|
|
|
Ureteral obstruction |
~80% |
~50% |
Rare |
Rare |
Rare |
Unknown |
Aortic displacement |
Rare |
Anterior |
|
|
|
|
Reactive perivascular lymphoid aggregates |
100% |
Absent |
Variable |
Rare |
Variable |
Present in the inflammatory type |
Necrosis |
Absent |
Variable |
Fat necrosis |
Rare |
Focal |
Fat necrosis |
Vasculitis |
~50% |
Absent |
Absent |
Absent |
Absent |
Absent |
Clonality |
Absent |
Variable |
Absent |
Absent |
Absent |
Present |
Β-catenin |
Negative |
Unknown |
Negative |
Positive in 90% of cases |
Negative |
Variable positivity |
ALK-1 |
Negative |
Usually negative |
Negative |
Negative |
Positive in 50% of cases |
Negative |
CD-117 |
Negative in spindle cell component |
Rare |
Variable |
Negative |
Rare |
Negative |
Desmin |
Negative |
Negative |
Variable |
Rare |
Usually positive |
Rare |
S100 |
Negative |
Negative |
Negative |
Rare |
Negative |
Usually positive in the adipocytic component |
Biopsy
A wide spectrum of fibroinflammatory disorders can mimic retroperitoneal fibrosis on imaging. Management strategies are diverse and depend strongly on the histological diagnosis and extent of the disease. Histology and immunohistochemistry are required to confirm the diagnosis.
The amount of tissue harvested via core needle biopsy may not be sufficient for the histological diagnosis. Therefore, open biopsy can ensure a definite histological diagnosis and is traditionally performed. However, it is associated with significant morbidity. Laparoscopic biopsy is safe, minimally invasive, cost-effective, and useful in making therapeutic decisions for retroperitoneal masses.
Tissue for histologic diagnosis can be obtained under CT or ultrasonographic guidance. In a 1999 publication, Dash et al described fine-needle aspiration for the diagnosis of retroperitoneal fibrosis, but most clinicians prefer a Tru-Cut needle biopsy. [53] In 1998, Pfammatter et al performed transcaval retroperitoneal core biopsies and suggested that the technique may have a role in patients at high operative risk, especially if the results from standard biopsies are inconclusive. [54]
-
Intravenous urogram in a patient with retroperitoneal fibrosis shows medial deviation of the middle part of both ureters.
-
Retrograde ureterogram in a patient with retroperitoneal fibrosis reveals smooth narrowing and medial shift of the ureter.
-
Retroperitoneal fibrosis. Retrograde pyelogram demonstrates hydronephrosis.
-
Retroperitoneal fibrosis. Contrast-enhanced CT scan demonstrates a periaortic soft tissue attenuating mass.
-
Retroperitoneal fibrosis. Noncontrast CT scan shows periaortic fibrotic reaction associated with an inflammatory aortic aneurysm. Note bilateral ureteric stents.
-
Management algorithm of retroperitoneal fibrosis.
-
Postureterolysis intravenous urogram in a patient with retroperitoneal fibrosis demonstrates lateral displacement of both ureters and a double J stent on the right side.
-
Retroperitoneal fibrosis. Retrograde pyelogram shows satisfactory positioning of a wall stent in a patient with postureterolysis obstruction.
-
Retroperitoneal fibrosis. Abdominal radiograph demonstrates a wall stent on the right side.
Tables
|
Retroperitoneal Fibrosis |
Retroperitoneal Lymphoma |
Sclerosing Mesenteritis |
Desmoid-Type Fibromatosis |
Inflammatory Myofibroblastic Tumor |
Well-Differentiated Liposarcoma Sclerosing Variant |
Ureteral displacement |
Medial |
Lateral |
|
|
|
|
Ureteral obstruction |
~80% |
~50% |
Rare |
Rare |
Rare |
Unknown |
Aortic displacement |
Rare |
Anterior |
|
|
|
|
Reactive perivascular lymphoid aggregates |
100% |
Absent |
Variable |
Rare |
Variable |
Present in the inflammatory type |
Necrosis |
Absent |
Variable |
Fat necrosis |
Rare |
Focal |
Fat necrosis |
Vasculitis |
~50% |
Absent |
Absent |
Absent |
Absent |
Absent |
Clonality |
Absent |
Variable |
Absent |
Absent |
Absent |
Present |
Β-catenin |
Negative |
Unknown |
Negative |
Positive in 90% of cases |
Negative |
Variable positivity |
ALK-1 |
Negative |
Usually negative |
Negative |
Negative |
Positive in 50% of cases |
Negative |
CD-117 |
Negative in spindle cell component |
Rare |
Variable |
Negative |
Rare |
Negative |
Desmin |
Negative |
Negative |
Variable |
Rare |
Usually positive |
Rare |
S100 |
Negative |
Negative |
Negative |
Rare |
Negative |
Usually positive in the adipocytic component |
